Skewing of the T-cell receptor repertoire in patients receiving rituximab after allogeneic hematopoietic cell transplantation: what lies beneath?

Abstract

Rituximab is known to affect T cell immune responses. We and others have reported expansions of T large granular lymphocytes (T-LGLs) in lymphoma patients after Rituximab. We report here the immunogenetic profiling of the T cell receptor (TR) gene repertoire in 14 patients who received Rituximab post allo-HCT and explore clinicobiological correlations. All experienced antigenic triggers, CMV, EBV re-activation and chronic GvHD and had been treated with Rituximab. Skewing of TRBV genes was observed: 3 TRBV genes accounted for half of the repertoire. Oligoclonal pattern with expanded clonotypes was common. Patients with oligoclonality exhibited frequently cGvHD. Longitudinal samples in one revealed distinct clonotypes, suggesting clonal drift. T-LGL leukemia of donor origin with mixed chimerism eventually developed. In conclusion, we report development of oligoclonal T-LGLs after Rituximab post allo-HCT, alluding to antigen selection. Persistence of this phenomenon likely reflects strong antigenic stimulation by viruses and/or cGVHD aggravated by Rituximab.

Keywords:

• Rituximab
• T LGL leukemia
• allo-HCT

Acknowledgments

This work was supported in part by the project ODYSSEUS which is implemented under the ‘Action for the Strategic Development on the Research and Technological Sector’, funded by the Operational Programme 'Competitiveness, Entrepreneurship and Innovation' (NSRF 2014-2020) and co-financed by Greece and the European Union (European Regional Development Fund); ‘MEDGENET, Medical Genomics and Epigenomics Network’ (H2020, No.692298) by the EU and the Horizon 2020 Framework Programme.

Potential conflict of interest

Disclosure forms provided by the author are available with full text for this article at https://doi.org/10.1080/10428194.2018.1543881.